Pathways Involved in Immune Regulation and B Cell Selection

参与免疫调节和 B 细胞选择的途径

• 批准号: MC_UU_00008/6
• 负责人: Richard Cornall
• 金额: $ 211.52万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00008%2F6
• 关键词: Pathways; Involved; Immune; Regulation; Cell

Our aim is to understand the genetics of immune disease in humans, and to develop new therapeutic strategies that can interrupt the development of autoimmunity. To understand how abnormal regulation of the immune system leads to autoimmune disease we are studying the cells involved in ‘immunological memory’ which is the basis for all vaccination strategies and leads to the development of long-term immunity to infectious disease. We have developed new methods of tracking cells and characterizing the events involved in generation of immunity and we are using these to study self tolerance to antigens inside cells – for example those involved in the autoimmune disease systemic lupus erythematosus (SLE). We have used a model to look for defects in the immune response to self and foreign antigens, and are linking genes with their biological outcomes. We have identified a protein called Roquin, as a potentially important protein in the development of rheumatoid arthritis and SLE and we are now working on molecules that could be used as a therapy to reduce the self-directed immune response in these two debilitating diseases.

我们的目标是了解人类免疫疾病的遗传学，并开发新的治疗策略来中断自身免疫的发展。为了了解免疫系统的异常调节如何导致自身免疫疾病，我们正在研究参与“免疫记忆”的细胞。这是所有疫苗接种策略的基础，并导致对传染病的长期免疫力的发展。我们开发了跟踪细胞和表征免疫产生所涉及事件的新方法，我们正在利用这些方法来研究对传染病的自我耐受性。细胞内的抗原——例如参与我们使用了一种模型来寻找对自身和外来抗原的免疫反应缺陷，并将基因与其生物学结果联系起来，它是一种潜在的重要蛋白质。蛋白质在类风湿性关节炎和系统性红斑狼疮的发展中发挥着重要作用，我们现在正在研究可用作治疗方法的分子，以减少这两种使人衰弱的疾病的自我定向免疫反应。

项目成果

B1a B cells require autophagy for metabolic homeostasis and self-renewal.

B1a B 细胞需要自噬来实现代谢稳态和自我更新。

• DOI: http://dx.10.1084/jem.20170771
• 发表时间: 2018
• 期刊: The Journal of experimental medicine
• 作者: Clarke AJ

High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation.

高通量表型分析揭示了免疫变异的广泛遗传和结构基础。

• DOI: http://dx.10.1038/s41590-019-0549-0
• 发表时间: 2020
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Abeler

An essential role for the Zn2+ transporter ZIP7 in B cell development.

Zn2 转运蛋白 ZIP7 在 B 细胞发育中发挥重要作用。

• DOI: http://dx.10.1038/s41590-018-0295-8
• 发表时间: 2019
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Anzilotti C

Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.

使用 DNA 纳米球图案阵列绘制小鼠器官发生的时空转录组图谱。

• DOI: http://dx.10.1016/j.cell.2022.04.003
• 发表时间: 2022
• 期刊: Cell
• 影响因子: 64.5
• 作者: Chen A

Dynamic regulation of hypoxia-inducible factor-1a activity is essential for normal B cell development.

缺氧诱导因子 1a 活性的动态调节对于 B 细胞的正常发育至关重要。

• DOI: http://dx.10.1038/s41590-020-0772-8
• 发表时间: 2020
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Burrows N